Myxedema Coma

Risk factors

• Long-standing hypothyroidism, often untreated or with poor adherence
• Elderly female, winter months, cold exposure
• Precipitants: infection (especially pneumonia, UTI, sepsis), MI, stroke, GI bleed, trauma, surgery
• Sedative or opioid administration in undiagnosed hypothyroidism
• Amiodarone, lithium, abrupt discontinuation of levothyroxine
• Hypothermic environmental exposure

Pathophysiology

Profound thyroid hormone deficiency reduces metabolic rate, cardiac output, thermogenesis, and respiratory drive. CNS depression, hypoventilation with CO2 retention, hypoglycemia, hyponatremia (impaired free water excretion), and decreased drug metabolism produce a self-perpetuating spiral.

Clinical presentation

Differential diagnosis

• Sepsis — Common precipitant — infection may be the trigger; obtain cultures and treat empirically
• Hypothermia from environmental exposure — May coexist; thyroid testing in any unexplained hypothermia
• Adrenal crisis — Often coexists; treat with stress-dose steroids BEFORE thyroid hormone
• Hepatic encephalopathy — Liver disease, asterixis, elevated ammonia
• Severe hyponatremia — Itself a feature of myxedema coma; correct cautiously
• Drug overdose / sedative ingestion — Tox screen; reversal agents as indicated
• Stroke — Imaging to exclude; presentation may overlap

Diagnostic workup

Diagnostic algorithm

flowchart TD
  A[Obtunded elderly patient<br/>+ hypothermia + bradycardia] --> B[Suspect myxedema coma<br/>± precipitant infection]
  B --> C[Send TSH/free T4, cortisol,<br/>cultures, ABG, lactate, BMP]
  C --> D[ABCs: intubate if needed<br/>Passive rewarm only]
  D --> E[Hydrocortisone 100 mg IV q8h<br/>FIRST]
  E --> F[Levothyroxine 200-400 mcg IV load<br/>then 50-100 mcg IV daily]
  F --> G[Treat precipitant<br/>empiric antibiotics]
  G --> H[ICU monitoring<br/>correct Na slowly, glucose, fluids]
  H --> I{Inadequate response?}
  I -->|Yes| J[Consider IV T3<br/>(liothyronine)]
  I -->|No| K[Transition to PO levothyroxine<br/>when stable]

Treatment

Complications

• Death (mortality 30-50%)
• Respiratory failure requiring prolonged ventilation
• Cardiac arrhythmia, pericardial effusion, tamponade
• Ileus, GI bleed
• Adrenal crisis if steroids omitted
• Cerebral pontine myelinolysis from rapid correction of hyponatremia

PANCE pearls

• Hydrocortisone BEFORE levothyroxine — always. Coexisting adrenal insufficiency is common and giving thyroid hormone first can precipitate adrenal crisis.
• Look for the precipitant — infection (pneumonia, UTI), cold exposure, MI, stroke, or sedative use. Treating only the thyroid will not save the patient.
• Passive rewarming only — active rewarming causes peripheral vasodilation and shock in these patients.
• Sodium correction must be slow (<8-10 mEq/L per 24 h) to avoid osmotic demyelination.
• Hypothermia in an obtunded elderly woman = check TSH while you check the cultures.

References

• ATA 2014 — Guidelines for the Treatment of Hypothyroidism — Myxedema Coma section (Jonklaas et al., Thyroid 2014)
• Mathew & Aronow 2011 — Myxedema Coma: A New Look into an Old Crisis (Mathew et al., J Thyroid Res 2011)
• Wartofsky 2006 — Myxedema Coma (Wartofsky, Endocrinol Metab Clin North Am 2006)